Evidence mapPaperPMID 35313030Full record

ArticleHepatology (Baltimore, Md.)2022

Hepatic kinome atlas: An in-depth identification of kinase pathways in liver fibrosis of humans and rodents.

Justin F Creeden, Zachary A Kipp, Mei Xu, Robert M Flight, Hunter N B Moseley, Genesee J Martinez, Wang-Hsin Lee, Khaled Alganem, Ali S Imami, Megan R McMullen and 8 more

Open access · greenAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Metabolites · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 2 countries.

Justin F CreedenDepartment of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.ORCID 0000-0003-3123-8401
Zachary A KippDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Mei XuDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Robert M FlightDepartment of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA.
Hunter N B MoseleyDepartment of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA.
Genesee J MartinezDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Wang-Hsin LeeDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Khaled AlganemDepartment of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
Ali S ImamiDepartment of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
Megan R McMullenDepartment of Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA.
Sanjoy RoychowdhuryDepartment of Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA.
Atta M NawabiDivision of Transplant and Hepatobiliary, Department of Surgery, The University of Kansas Medical Center, Kansas City, Kansas, USA.
Jennifer A HippStrata Oncology, Ann Arbor, Michigan, USA.
Samir SofticDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Steven A WeinmanDepartment of Internal Medicine and Liver Center, University of Kansas Medical Center, Kansas City, Kansas, USA.
Robert McCullumsmithDepartment of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
Laura E NagyDepartment of Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA.
Terry D HindsDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA.ORCID 0000-0002-7599-1529
University of Kentucky · USCleveland Clinic · USUniversity of Toledo · USUniversity of Kansas Medical Center · USNeurosciences Institute · USStratasys (Israel) · IL

Funding

longitudinal assessment of stress and stress-related concepts across a behavioral weight loss interventionP20GM144269 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 to 2025
$7.6M
Project 4 Title: Innate immunity and cell death in ALDP50AA024333 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · 2021 to 2025
$5.0M
Translational assessment of brain bioenergetic function in schizophreniaR01MH121102 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI Christopher Marano, Robert E McCullumsmith · 2021 to 2024
$2.9M
University of Kentucky Markey Cancer Center – Cancer Center Support GrantP30CA177558 · UNIVERSITY OF KENTUCKY · 2025 to 2025
$2.8M
Development of Attenuated Furoxans as Novel Therapies for Alzheimer's DiseaseR01AG057598 · NIA · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI Isaac T Schiefer · 2022 to 2022
$386k
NCI NIH HHS P30 CA177558NIAAA NIH HHS P50 AA024333NIA NIH HHS R01 AG057598NIDDK NIH HHS R01 DK121797NIGMS NIH HHS P20 GM144269NIMH NIH HHS R01 MH107487NIMH NIH HHS R01 MH121102
6 · The paper itself

Abstract

BACKGROUND AND

aimsResolution of pathways that converge to induce deleterious effects in hepatic diseases, such as in the later stages, have potential antifibrotic effects that may improve outcomes. We aimed to explore whether humans and rodents display similar fibrotic signaling networks. APPROACH AND

resultsWe assiduously mapped kinase pathways using 340 substrate targets, upstream bioinformatic analysis of kinase pathways, and over 2000 random sampling iterations using the PamGene PamStation kinome microarray chip technology. Using this technology, we characterized a large number of kinases with altered activity in liver fibrosis of both species. Gene expression and immunostaining analyses validated many of these kinases as bona fide signaling events. Surprisingly, the insulin receptor emerged as a considerable protein tyrosine kinase that is hyperactive in fibrotic liver disease in humans and rodents. Discoidin domain receptor tyrosine kinase, activated by collagen that increases during fibrosis, was another hyperactive protein tyrosine kinase in humans and rodents with fibrosis. The serine/threonine kinases found to be the most active in fibrosis were dystrophy type 1 protein kinase and members of the protein kinase family of kinases. We compared the fibrotic events over four models: humans with cirrhosis and three murine models with differing levels of fibrosis, including two models of fatty liver disease with emerging fibrosis. The data demonstrate a high concordance between human and rodent hepatic kinome signaling that focalizes, as shown by our network analysis of detrimental pathways.

conclusionsOur findings establish a comprehensive kinase atlas for liver fibrosis, which identifies analogous signaling events conserved among humans and rodents.

Indexed as

Liver DiseasesReceptor, InsulinAnimalsCollagenDiscoidin Domain ReceptorsFibrosisHumansLiverLiver CirrhosisMiceProtein KinasesRodentiaSerineThreonineCollagenDiscoidin Domain ReceptorsProtein KinasesReceptor, InsulinSerineThreonine

Identifiers

PMID35313030
PMCPMC9489820
OpenAlexW4220904794

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.